Liver Fibrosis, Metabolic Dysfunction-Associated Steatohepatitis (MASH), Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Conditions
Keywords
Navy beans, Dietary intervention, Isocaloric substitution, Gut microbiome, Gut-liver axis, Liver stiffness
Brief summary
This study is a 24-week randomized crossover feasibility trial evaluating an isocaloric navy-bean dietary substitution in 40 adults with metabolic dysfunction-associated steatotic liver disease (MASLD) and intermediate-stage (F2-F3) fibrosis. Participants are randomized to one of two sequences-habitual diet followed by a navy-bean-rich diet, or a navy-bean-rich diet followed by habitual diet-with each 12-week phase guided by registered dietitians so that navy beans replace an equivalent caloric load without changing total energy intake. The primary aim is to establish feasibility and acceptability, measured by recruitment and retention, adherence with biomarker (plasma pipecolic-acid) concordance, and patient acceptability.
Detailed description
Rationale: Diet acts on MASLD progression through the gut-liver axis, in which microbial composition, intestinal barrier integrity, and microbe-derived metabolites influence hepatic inflammation, steatosis, and fibrosis. Navy beans supply fermentable fiber, resistant starch, and polyphenols that nourish short-chain-fatty-acid-producing microbes, and prior human work (the BE GONE trial) demonstrated increased microbial diversity, enrichment of beneficial taxa, and favorable metabolomic and proteomic shifts following an 8-week navy-bean intervention. An isocaloric substitution approach isolates bean-specific biologic effects from weight change, addressing a major confounder in MASLD dietary trials.
Interventions
OTHERDietary Supplement/Behavioral: Navy Bean-Rich Diet
Isocaloric substitution in which navy beans replace an equivalent caloric load of the habitual diet under individualized registered-dietitian counseling, with resting-metabolic-rate-based prescription and a gradual dose ramp-up (½ to 1 cup). Total energy intake is maintained.
Participants maintain their usual diet without the navy-bean substitution during the assigned control period
Sponsors
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
SINGLE (Outcomes Assessor)
Masking description
with blinded central imaging reads and blinded outcome/laboratory assessment
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Adults 18-75 years of age with capacity to provide informed consent * Clinical diagnosis of MASLD, confirmed by imaging (MRI-PDFF or VCTE) or prior liver biopsy. * Intermediate-stage fibrosis (F2-F3) confirmed by one of the following (most recent qualifying result): VCTE (FibroScan) 8.0-14 kPa, MRE 3.0-4.6 kPa (2D EPI @ 60 Hz), or liver biopsy read as F2-F3 * Body mass index 25-45 kg/m² * Stable medications for ≥12 weeks for diabetes, hypertension, dyslipidemia, or weight management * Alcohol intake below MASLD thresholds (≤15 drinks/week for men, ≤10 drinks/week for women) * Willing and able to consume study navy beans and complete dietary recalls (ASA-24/DSQ) * Able to undergo MRI and MRE (no contraindications) and attend study visits * Agrees to biospecimen collection (blood, stool, saliva) and patient-reported outcomes
Exclusion criteria
* Other chronic liver disease (hepatitis B, hepatitis C, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, primary biliary cholangitis, primary sclerosing cholangitis) * Decompensated liver disease (ascites, variceal bleeding, encephalopathy) or Child-Pugh B/C cirrhosis, or clinical portal hypertension/decompensation * Heavy alcohol use above MASLD thresholds, or alcohol use disorder within 12 months * Legume/bean allergy or intolerance * Initiation or dose change of antidiabetic, lipid-lowering, antihypertensive, or weight-loss medications within the past 12 weeks, or anticipated changes during the trial * Recent initiation of agents known to affect hepatic fat or fibrosis (e.g., GLP-1 receptor agonist, SGLT2 inhibitor, pioglitazone, resmetirom) within 12 weeks * Use of hepatotoxic drugs likely to confound liver enzymes in the prior 12 weeks (per investigator judgment) * New supplements targeting weight loss, liver health, or the microbiome within 8-12 weeks (e.g., berberine, high-dose omega-3, pre/probiotics) * Antibiotics, probiotics, or colonoscopy preparation within 8 weeks * Planned bariatric surgery or other major weight-loss intervention during the study * Recent weight change \>5% within 8-12 weeks prior to baseline * Severe gastrointestinal disease (inflammatory bowel disease, celiac disease, short bowel syndrome) that may impair tolerance * Uncontrolled diabetes (HbA1c \>10%), severe renal dysfunction (eGFR \<45), or unstable cardiovascular, thyroid, or psychiatric illness * Pregnant or breastfeeding * Contraindications to MRI (e.g., non-compatible implants, severe claustrophobia) * Participation in another interventional study within the last 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility composite score | Week 24 | Feasibility is assessed as a composite of three pre-specified measure 1. Recruitment velocity: number of participants randomized per month, calculated as total randomized divided by months of active enrollment. 2. Retention at Week 24: proportion of randomized participants completing both 12-week crossover periods and the Week-24 visit within the protocol window, calculated as number retained divided by number randomized. 3. Adherence with biomarker concordance: proportion of participants achieving ≥75% of prescribed navy-bean servings during the navy-bean phase with plasma pipecolic-acid concordance, calculated as number adherent-and-concordant divided by number evaluable. Each component is scored 0 (below threshold), 1 (intermediate), or 2 (meets target) against pre-specified progression criteria, and the three are summed. The composite score ranges from 0 to 6, with higher scores indicating greater feasibility. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants rating the navy-bean intervention as acceptable | At Week 12 and Week 24 | Proportion of participants rating the navy-bean intervention as acceptable, defined as a score ≥4 on a 5-point Likert scale (minimum 1 = least acceptable, maximum 5 = most acceptable; higher scores indicate greater acceptability) assessing taste, tolerability, and convenience. |
| Proportion of visits with Isocaloric fidelity | through Week 24 | Proportion of visits at which energy intake is within ±5% of the prescribed target with body-weight change ≤2% per period, calculated from dietary recalls and serial weights. Higher values indicate better maintenance of isocaloric substitution. |
| Change in hepatic fat by MRI-PDFF | Baseline (Week 0), Week 12, and Week 24 | Within-person difference in hepatic fat, measured as MRI proton density fat fraction (percent) from blinded central reads, comparing the navy-bean condition to the habitual condition. Lower MRI-PDFF indicates less hepatic steatosis. |
| Change in alanine aminotransferase (ALT) | Baseline (Week 0), Week 12, and Week 24 | Serum ALT (U/L) levels. Lower ALT indicates less hepatocellular injury. |
| Change in liver stiffness by MRE | Baseline (Week 0), Week 12, and Week 24 | Liver stiffness (kPa) by magnetic resonance elastography. Lower stiffness indicates less fibrosis burden. |
Countries
United States
Contacts
CONTACTXiaotao Zhang, MD, PhD
CONTACTMeena Bansal
PRINCIPAL_INVESTIGATORXiaotao Zhang, MD, PhD
Icahn School of Medicine at Mount Sinai
Outcome results
None listed